Study of urinary proteomes in Anderson-Fabry disease

Abstract

Background: Anderson-Fabry disease (AFD) is an X-linked genetic disorder with deficient a-galactosidase A activity. The main aim of this work was to investigate possible differences in urine proteins between healthy controls and AFD patients and to identify abnormal proteins as potential biomarkers of disease. Material and methods: We studied 2D electrophoresis images of urine samples collected from AFD patients and healthy subjects. The proteins were separated using isoelectric focusing method followed by SDS-PAGE. The proteins were then visualized by silver staining and characterized by matrix-assisted laser desorption/ionization time-of-flight mass spectrometry (MALDI-TOF MS). Results: We found out that the urinary spectra of all the Fabry disease samples included identical proteins with molecular weight around 20-40 kDa. The concentration of some proteins was more than three times higher in the AFD samples, compared to the controls. The abundant proteins were identified by MALDI-TOF MS and included the following: alpha-1-antitrypsin, alpha-1-microglobulin, prostaglandin H2 D-isomerase, complement-c1q tumor necrosis factor-related protein, and Ig kappa chain V-III. Possible glycosylation at Asn51 and Asn78 sites of the prostaglandin H2 D-isomerase was detected. Conclusions: AFD urinary proteomics revealed increased secretion of several proteins. We postulate that the observed difference in the amount of prostaglandin H2 D-isomerase and its position on twodimensional gels might be related to different glycosylation in AFD subjects.

A Distinct Urinary Biomarker Pattern Characteristic of Female Fabry Patients That Mirrors Response to Enzyme Replacement Therapy

“…Moore et al [18] compared serum samples of 12 male and 1 female pediatric Fabry patients before and after 6 months of ERT by LC-MS/MS and found 5 of 50 identified proteins to be significantly altered under therapy. Vojtova et al [19] compared 11 male and 9 female Fabry patients with or without ERT to 10 healthy controls using 2DGE followed by MALDI-TOF/TOF and identified 5 differentially expressed proteins. However, none of the above mentioned studies validated their results in an independent cohort.…”

Urinary β-trace protein

“…In fact, literature data indicate a higher urinary excretion of BTP in hypertensive patients, increasingly along with advance in renal dysfunction, in diabetic patients with subclinical renal injury or with cardiovascular complications, in lupus nephritis patients according to the activity of disease and efficacy of treatment, and also in Anderson–Fabry disease. [36–43] …”

Biomarkers and Imaging Findings of Anderson–Fabry Disease—What We Know Now

“…Vojtová et al found that the AFD does not lead to the formation of new proteins or degradation products, although quantitative changes were found in urine such as: substantially increased Ig kappa chain V-III, complement-C1q tumour necrosis factor-related protein and prostaglandin H2 d -isomerase [55]. …”